Chapter42AntimicrobialAgents.ppt

Chapter42AntimicrobialAgents,A/PZhi-ZhongXie,Ph.D.,SectionChemotherapeuticdrugs,ntimakrobil抗菌剂,kemu,erpju:tik化疗药物,Maincontents,CommontermsofantibacterialagentsThemechanismsofactionofantibacterialagentsBacterialresistanceApplicationprincipleofantibacterialagents,ntimakrobil,SomeBasicConcepts,Chemotherapy：Itisdefinedaspharmacotherapyfordiseasescausedbyavarietyofpathogens,includingpathogenicmicroorganisms(bacteria,fungi,viruses),parasiteandcancer.Chemotherapeuticdrugs:anti-pathogenicmicroorganism,anti-parasite,andanti-tumordrugs.Anti-pathogenicmicroorganismdrugsincludeantibacterialagents,anti-viralagentsandanti-fungalagents,pdnk,makrorgn,zm,抗病原微生物,Aboutbacteria,Bacteriaisdifferentinmorphology,structure,growthcharacteristicsanddyeingproperty.Soitcanbeclassifieduponthesedifference,likecoccus,bacillus,spirilla,etc.BacteriaisusuallyclassifiedintoGrampositivebacteriaandGramnegativebacteriabaseonthedifferenceofthestructureofcellwall.,sprl螺旋菌,mrfldi形态学,kks球菌,bsls杆菌,Gram-positivebacteriaGram-positivecocciGram-positivebacilli,Medicallyrelevantgram-negativecocciincludethethreeorganismsthatcausetransmitteddiseases(Neisseriagonorrhoeae),ameningitis(Neisseriameningitidis),andrespiratorysymptoms(Moraxellacatarrhalis).Gram-negativebacilliincludeSalmonella,Escherichia,Pseudomonas,Bacteroides,Shigella,Proteus,Enterobacter,Citrobacter,Serratia,Yersiniaspecies,etc.,Gram-positivecoccusincludeDiplococci,likeStreptococcuspneumoniaeandNeisseriagonorrhoeae,StreptococcilikeStreptococcuspyogenes,StaphylococcilikeStaphylococcusaureus.Gram-positivebacilliincludeClostridium,Corynebacterium,Listeria,Propionibacterium,etc.,Gram-negativebactariaGram-negativecocciGram-negativebacilli,bsilai,Theclassificationofbacteria,:rs,Pharyngolaryngitisfrlrndats,furuncleandcarbuncle,stflkks,slmnl沙门氏菌属、,erikj埃希氏杆菌属、,psju:dumns假单胞菌属、,bktridi:z拟杆菌属、iel志贺氏菌属、prutju:s变形杆菌属、,entrubkt肠杆菌属、,Antibacterialspectrum,Narrow-spectrumantibioticsG+:-lactamantibiotics(Naturalpenicillins:PenicillinG,Firstgenerationcephalosporins),FirstgenerationMacrolides,LincomycinAnotherwayistouseotherdrugsinstead.,2.Alterationoftarget,Mechanismofdrugresistance,trnspeptdes转肽酶,peptdglaknsnss,dosd,Qualitativechange:Theresistancemaybeduetothedrugbindingsitemutationofthetargetgene,includingpointmutationandcompletemutationofthetarget.Pointmutationleadstolowaffinityofadrugtoitstarget.ThepointmutationofDNAgyraseortopoisomerasegeneresultsinresistancetofluoroquinolone;themutationofribosomeresultsinresistancetoaminoglycosides,themutationoftranspeptidasesleadstoresistancetopenicillins.,2.Alterationoftarget,Mechanismofdrugresistance,tpismreiz,2.Alterationoftarget,Qualitativechange:Thecompletemutationofthetargetleadstolossofaffinityofadrugtoitstarget.Forexample,staphylococciareresistancetomethicillin,oneofpenicillins.Theyproduceanewkindoftranspeptidasetowhichmethicillincannotbind.Theysubstitutearesistantalternativeforthenative,susceptibletarget.,Mechanismofdrugresistance,stfiluksi葡萄球菌,trnspeptdes,Inaword,alterationoftargetmaycausereducedbindingofadrugtothecriticaltargetorsubstitutionofanewtargetthatdoesnotbindtothedrugforthenativetarget.,2.Alterationoftarget,Mechanismofdrugresistance,3.Thedrugdoesnotreachitstarget,Mechanismofdrugresistance,Therearetwocases,oneispermeabilityalterationofoutermembrane,anotheriseffluxofdrug.Decreasedpermeabilityofoutermembranecanreducethedrugentryintothebacterialcells.ThismechanismofresistanceisspecificforG-bacteria,becausetheircellwallshaveoutermembraneinadditiontopeptidoglycan.,pmblti,peptdglakn肽聚糖,Mechanismofdrugresistance,TheoutermembraneofG-bacteriaisapermeabilitybarrierthatexcludeslargepolarmoleculesfromenteringthecell.Smallpolarmolecules,includingmanyantibiotics,enterthecellthroughchannelsmadeupofproteinscalledporins.Absenceof,mutationin,orlossoftheappropriateporinchannelcanslowtherateofdrugentryintothecellorprevententryaltogether,reducingtheeffectivedrugconcentrationatthetargetsite.,3.Thedrugdoesnotreachitstarget,prn孔蛋白,Mechanismofdrugresistance,Bacteriaalsohaveeffluxpumpsthatmaytransportdrugsoutofthebacterialcells.Resistancetotetracyclineandto-lactamantibioticsisanexampleofaneffluxpumpmechanism.,3.Thedrugdoesnotreachitstarget,ttrsakln,ntbatks,Maincontents,CommontermsofantibacterialagentsThemechanismsofactionofantibacterialagentsBacterialresistanceApplicationprincipleofantibacterialagents,Applicationprincipleofantibacterialagents,TrytomakeadefinitivediagnosisSelectaneffectivedrugrationallyApplyappropriatedosageanddurationApplycombineddrugtherapyrationally,Applicationprincipleofantibacterialagents,Somespecialdistributionsofdrugsishelpfultothetreatmentofsomespecificsiteinfections.e.g.Newmacrolides(likeroxithromycinandClarithromycin)aremoreusedinupperrespiratorytractinfectionthanPenicillinG,Lincomycinpeoplevisitingareaswheremalariaexistsusuallystarttakingpyrimethamineonetotwoweeksbeforearrivingandcontinuetakingthemforfourweeksafterleaving;Surgicalantimicrobialprophylaxis,menindaitis,parmemin乙胺嘧啶,rfmpn,m,nikkl脑膜炎球菌性脑膜炎,ntmakrbl,Surgicalantimicrobialprophylaxishasbeenshowninmanyrandomizedclinicaltrialstoreducetheincidenceofpostoperativewoundinfections.Especiallyin:Patient-relatedriskfactorsCertainvalvularheartdisordersImmunosuppressionStreptococcifromthemouth,enterococcifromtheGIorgenitourinarytract,andstaphylococcifromtheskincommonlyenterthebloodstreamandmayadheretoanabnormalordamagedvalvesurface,producingendocarditis.,Surgicalantimicrobialprophylaxis,AcuteInfectiousEndocarditis,endukdaitis心内膜炎,s:rdkl,proflkss,rnd,maizd随机,pstprtv术后,mjunosprn免疫抑制,streptukksai链球菌,entrkka肠球菌,Applicationprincipleofan